Activation of the Leukemia Plasmacytoid Dendritic Cell Line PMDC05 by Toho-1, a Novel IDO Inhibitor

作者：Yamahira Akie; Narita Miwako; Iwabuchi Minami; Uchiyama Takayoshi; Iwaya Shunpei; Ohiwa Rie; Nishizawa Yoshinori; Suzuki Takafumi; Yokoyama Yusaku; Hashimoto Shigeo; Takizawa Jun; Sone Hirohito; Takahashi Masuhiro^*

来源：Anticancer Research, 2014, 34(8): 4021-4028.

• Novel IDO inhibitor
• Toho-1
• leukemic plasmacytoid dendritic cell line
• PMDC05
• antigen-presenting ability
• CTL-inducing ability
• Necrostatin-1 (R)

Background/Aim: Indoleamine-2,3-dioxygenase (IDO) is a rate-limiting enzyme for tryptophan metabolism and plays an immunosuppressive role. Antigen-presenting cells, when activated, increase the expression of IDO, which results in the suppression of subsequent immune reaction. A novel IDO inhibitor, Toho-1, was explored for its applicability to immunotherapy. Materials and Methods: We investigated the effects of Toho-1 on antigen presentation and antigen-specific cytotoxic T-lymphocyte-inducing ability of leukemia plasmacytoid dendritic cell line PMDC05, which was established in our laboratory. Results: While antigen presentation-associated molecules in PMDC05 cells were increased by stimulation with lipopolysaccharide and interferon-gamma, IDO mRNA and protein expression were also enhanced. Such treatment of PMDC05 cells in combination with Toho-1 enhanced the antigen-presenting and CTL-inducing ability of PMDC05 cells. Conclusion: These findings suggest the ability of Toho-1 to potentiate antigen-presenting cells and its applicability in immunotherapy of cancer.

• 出版日期2014-8